CMT 1A axonal atrophy research from U of Genova

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Research from J Peripher Nerv Syst. 2004 Jun;9(2):111.

Expression of ciliary neurotrophic factor (CNTF) in charcot-marie-tooth

type 1A (CMT1A) disease.

Vigo T, Schenone A, Mancardi G, Abruzzese M, Timmerman V, Van Hummelen

P, Nobbio L.

Department of Neuroscience, Ophthalmology and Genetics, University of

Genova.

cDNA microarray experiments on sciatic nerves from 30-day-old PMP22

transgenic (PMP22tg) rats were performed to detect genes modulated in

CMT1A. Among the downregulated genes, CNTF mRNA was significantly

reduced, whereas other neurotrophic factors (BDNF, NT3, NGF) and cognate

receptors (TRKA, TRKB, TRKC) were unchanged. We further studied CNTF

expression in transgenic nerves using an ELISA technique. We observed

significantly (p < 0.001) lower concentrations of the protein in sciatic

nerves from homozygous (59 +/- 7.8 pg/mg of proteins) and heterozygous

(140.8 +/- 17.56 pg/mg of proteins) PMP22tg nerves compared to normal

controls (713.8 +/- 168.7 pg/mg of proteins). Moreover, using real time

PCR, we studied CNTF expression in human sural nerves from 2 CMT1A

patients and in 3 control nerves. According to the animal results, CNTF

mRNA expression was absent in CMT1A patients whereas it was detectable

in control nerves (1.99 +/- 0.9). Finally, we studied CNTF mRNA

expression in aging PMP22tg rats; preliminary results show a further

decrease of CNTF mRNA in heterozygous transgenic rats compared to normal

age-matched littermates. Our results suggest that reduced CNTF

expression may account for the development of axonal atrophy in CMT1A.